A malignant neoplasm that contains elements of carcinoma (cancer of epithelial tissue, which is skin and tissue that lines or covers the internal organs) and sarcoma (cancer of connective tissue, such as bone, cartilage, and fat) so extensively intermixed as to indicate neoplasia of epithelial and mesenchymal tissue.

1. Carcinosarcoma 1

2. Abstract Carcinosarcoma is a very rare, aggressive tumour composed of epithelial and stromal components which both fulfill criteria of malignancy. This presentation is based on a case of carcinosarcoma which was located in the left side buccal mucosa of a 70 year old male patient who was presented to DHP and then treated with surgical resection of the lesion and neck dissection. 2

3. INTRODUCTION 3

4. CARCINOSARCOMA malignant neoplasm that contains elements of carcinoma and sarcoma, extensively intermixed as to indicate neoplasia of epithelial and mesenchymal tissue. Source: National Institute of Health-USA 4

5. EPITHELIAL COMPONENT Undifferentiated SCC Squamous cell carcinoma Poorly differentiated adenocarcinoma It may also include , Adenoid cystic carcinoma Epithelial myoepithelial carcinoma Salivary duct carcinoma. 5

6. NON-EPITHELIAL COMPONENT. Undifferentiated spindle cell sarcoma Other reported sarcomatous elements include, Fibrosarcoma Osteosarcoma Leiomyosarcoma Liposarcoma Follicular dendritic cell sarcoma Undifferentiated sarcoma Myxoid sarcomas Rhabdomyosarcoma Chondrosarcoma 6

7. Incidence inside the oral cavity Extremely rare Few cases had been reported Tongue Gingivae Floor of the mouth Buccal mucosa 7

8. Aggressive nature of the tumor Undergo Rapid growth Difficulty of complete surgical removal due to, Lack of demarcati0n between normal and pathological tissues Invasion. 8

11. Radiotherapy9

12. Case report 10

13. A 70 year old male presented with a swelling on left side cheek for 3months duration. 11

14. Complain of : Patient was referred from ++++++Hospital due to a growth on left side cheek. History of presenting complaint : Patient noticed a small lump on the L/S cheek 3 months back. It grew rapidly. Patient visited to +++++++ hospital ,from there he was referred to DHP. 12

15. Past Medical History : No abnormality detected Past Dental History : No Significant past dental history Social History : Married Father of a 2 children Supervisor at a tea estate 13

16. Habits : Chewing betel for 20-30 years 4-5 quids per day with all ingredients Family History : No relevant family history 14

17. Examination General Patient was distressed Extra oral examination Inspection : No significant findings Palpation : Firm swelling on L/S cheek Intra oral examination : 2 lesions 15

18. Major lesion Site : Left side cheek Size : 3×2×1.5cm Shape : More or less oval in shape Colour: Brownish to Gray in colour Consistency : Firm Non tender Pedunculated mass 16

19. Anterior cheek lesion Site : extend to Lt side commissural region Size : 1×1.5cm in size Margins : elevated margins with irregular surface Ulcerated Indurated 17

20. Provisional Diagnosis Squamous cell carcinoma 18

21. Special investigations 19

22. Ultra sound scan of Neck Multiple reactive lymph nodes in Lt side level I & II No evidence of metastasis 20

23. Biopsy Multiple incisional biopsies from major lesion,base of the major lesion & anterior cheek lesion were taken under GA & sent for histopathological investigations. 21

24. Histopathological Findings 22

26. Composed of spindle cells with increased mitosis.

27. Few duct like structures lined by dysplastic epithelium within the tumour23

28. Specimen from anterior cheek lesion & base of the major lesion - islands of squamous cell carcinoma invading in to superficial corium 24

29. Squamous cell Ca. Spindle cell Sarcoma 25

30. Squamous cell Ca. 26

32. Ductal component: cytokeretin positive, S100 negative27

33. Actin Positive Spindle cell component 28

34. 29 Cytokeratin Positive

35. These histopathological and immunohistochemical features are consistent with those of Carcinosarcoma 30

36. Management Lt. cheek resection & reconstructed with forehead flap Partial alveolectomy of Lt side jaw Supraomohyoid block dissection Specimens were sent for histopathologicalinvestigatigations. 31

37. Postoperative period On the 12th post operative day patient had developed a salivary fistula. On 18th post operative day Falp revision was done under LA. Patient has been discharged. 32

38. Carcinosarcoma Discussion 33

39. Carcinosarcoma Definition A malignant neoplasm that contains elements of carcinoma (cancer of epithelial tissue, which is skin and tissue that lines or covers the internal organs) and sarcoma (cancer of connective tissue, such as bone, cartilage, and fat) so extensively intermixed as to indicate neoplasia of epithelial and mesenchymal tissue. Source: National Institute of Health-USA 34

40. Synonyms Carcinosarcoma(Minkleret.al. 1970) Spindle-cell carcinoma or Pleomorphic Carcinoma(Ellis & Corio 1980,Zarbo et.al. 1986,Ellis et.al. 1987) Spindle-cell SCC Pseudosarcoma(Lane 1957) True malignant mixed tumour Sarcomatoid carcinoma 35

41. Classification 36

42. Squamous cell carcinoma (SCC) is an epithelial malignancy with morphologic features of squamous cell differentiation without additional features suggestive of other differentiated tissues. 37

43. Variants of squamous cell carcinoma (SCC) frequently arise within the mucosa of the upper aero digestive tract, accounting for up to15% of SCCs in these areas. Spindle cell/ Sarcomatoid Ca 38

44. Each of these variants has a unique histomorphologic appearance, which raises a number of different differential diagnostic considerations. 39

45. Epidemiology 40

46. Extremely RARE. Head-and-neck sites ; in descending Frequency Larynx Oral cavity Hypopharynx and pyriform sinus Sinonasal tract Oropharynx 41

47. Carcinosarcoma (CS) is sometimes found in other parts of the body. Incidence is more common in the upper body, particularly the lungs 42

48. In oral cavity carcinosarcoma can arise from either salivary glands or oral mucosa. 43

49. 44

50. Aetiology Idiopathic Radiation /trauma has been emphasized by some authors (Green & Bernier 1959) Accumulation of genetic mutations could be a factor. 45

51. Clinical Features 46

52. Symptoms are often present for a short duration Nearly all cases are described or received as; - Polypoid masses . - Mean size of about 2.0cm - Frequently ulcerated. - With a covering of fibrinoid necrosis. - Firm and fibrous cut surface. (Similar to conventional SCC, most tumours are T1 lesions at presentation.) 47

53. These carcinosarcomas occur most frequently on the lower lip,tongue and alvelolar ridge in either polypoid,exophytic or endophytic configurations. Surface ulceration is common with these tumors. As with any ulcerated lesion, these are likely to be infected and therefore may exude pus or contain abscess formation. Cervical lymphadenopathy is infrequent,distant metastasis may/not present. 48

54. Investigations 49

56. CT

57. Scintigraphy

58. Histopathological investigations;- Incisional biopsy - Excisional biopsy - Immunohistopathological investigations. 50

59. Ultra sound scanning to detect lymph node involvement. Chest X-ray & Gastroendoscopy to detect distant metastases. 51

60. HISTOLOGY 52

62. Usually Sarcomatous component is predominent.53

63. Biphasic presentation Ulcerated Carcinomatous component is either blended or in transition with sarcomatous component. Hypercellularity Variable patterns of spindle-cell growth in sarcomatous component Pleomorphism Increased mitotic figures 54

64. Carcinomatous component is usually Undifferentiated SCC Squamous cell carcinoma Poorly differentiated adenocarcinoma It may also include Adenoid cystic carcinoma Epithelial myoepithelial carcinoma Salivary duct carcinoma. 55

65. The sarcomatous component is usually, Undifferentiated spindle cell sarcoma Other reported sarcomatous elements include Fibrosarcoma Osteosarcoma Leiomyosarcoma Liposarcoma Follicular dendritic cell sarcoma Undifferentiated sarcoma Myxoid sarcomas Rhabdomyosarcoma Chondrosarcoma 56

66. Areas of squamous differentiation are most consistently identified at the base of the polypoid lesion, at the advancing margins, or within invaginations at the surface where the epithelium is not ulcerated or denuded.(Condition is same in our patient) CS will often present with little invasion into the underlying stroma, as it is polypoid. 57

67. Extensive infiltration and tissue destruction are common, as is perineural invasion and angioinvasion. Lymphatic spread is less common.Metastases to other sites or lymph nodes may show the carcinomatous or the sarcomatous components alone, or they may be mixed. 58

68. Compare with our patient; 59

69. So its extremely difficult in making the correct diagnosis of this tumor from a small biopsy specimen. It is well illustrated by varies diagnoses based on biopsy specimens. 60

70. Immunohistochemistry 61

71. Immunohistochemical markers are used in aid of diagnosis. Eg; -Cytokeratin - Vimentin - S-100 - Actin 62

72. Cytokeratins are proteins of keratin-containing intermediate filaments found in the intracytoplasmic cytoskeleton of epithelial tissue.there fore carcinomatouscomponentwhich is derived from epithelial tissue is strongly positive for cytokeratin Vimentin is a member of the intermediate filament family of proteins that is especially found in connective tissue. This filament is used as a marker for mesodermally derived tissues, and as such can be used as an immunohistochemical marker for sarcomas. 63

73. Immunohistochemistry for smooth muscle actin & vimentin reveals positivity in spindle cell component while the squamous cell component shows cytokeratin positivity. S-100 is negative. 64

74. Our patient’s immunohistochemical profile 65

75. HISTOPATHOGENISIS 66

76. Two antithetical hypotheses have been advanced to explain the histogenesis of carcinosarcomas: Multiclonal origin/ convergence hypothesis-arising from two or more stem cells Monoclonal origin/ Divergence hypothesis-from a single totipotential stem cell that differentiates in separate epithelial and mesenchymal directions. Recent immunohistochemical and chromosomal analyses appear to have settled this argument in favour of the monoclonal hypothesis. 67

77. But some of the cases showed a sharp demarcation between the carcinomatous & sarcomatous elements without transition zone & different immunohistochemical staining pattern of the two components for epithelial & mesenchymal markers which suggests a different cell origin for each tumor cell types. 68

78. However possibility remains that the demarcation may not signify a different origin, since carcinoma components are demarcated in some sarcomatoid carcinomas in which the sarcomatous component derives frommetaplasiaof the epithelial cells. 69

80. The role of the chemotherapy has not been established, but it maydecrease the incidence of recurrence or metastasis of primarily sarcomatous tissue. 71

81. Prognosis Mean survival time of those dead of the disease is 2 years. No clinical or histomorphological characteristic other than distant metastasis was found to be a reliable prognostic indicator. 72

82. Summery A 70 years old male presented with a rapidly growing swelling on left side cheek for 3months duration,and treated by surgical excision,was diagnosed as Carcinosarcoma. 73